Retinopathy of prematurity (ROP) remains the most frequent ocular cause of pediatric bilateral visual impairment. Whether ROP is mild or so severe that it requires treatment, many ROP patients suffer poor vision and risk of later eye and vision problems. We discovered that although mild deficits in rod photoreceptor function persist, function of the post-receptor retina recovers in mild, untreated ROP but not in severe, treated ROP. In this project, we will use complementary electroretinographic (ERG), psychophysical, and imaging methods to study the photoreceptors and post-receptor retina and its vasculature. We hypothesize that reorganization of post-receptor retinal circuitry and its vasculature is the basis for recovery in mild ROP and that in more severe ROP, compromised neurovascular plasticity precludes remodeling. As a corollary, we predict that the post-receptor retina places significant constraints on scotopic and photopic visual thresholds. To test our hypothesis, we will study ROP subjects in early infancy and follow them longitudinally to age 4 years; older subjects, age 10 to 20 years, will be studied in a cross-sectional design. Evaluation of retinal function will include ERG measures of rod and cone photoreceptor and post-receptor sensitivity and psycho-physical investigation of receptor and post-receptor function at 4 to 10 weeks and 4 years. At intervening ages, retinal function will be tracked using psychophysical tests of dark adapted thresholds and background adaptation. The hypothesis predicts normalization of post-receptor function in mild ROP but not in more severe ROP. Parameters of the retinal vasculature (tortuosity, diameter, distribution) will be quantified using image analysis of fundus photographs in all subjects, and in older subjects using adaptive optics (AO) imaging. The foveal pit and retinal layer thickness will be assessed using optical coherence tomography (AO-OCT), and extrafoveal cone packing geometry will be studied using scanning laser ophthalmoscopy (AO-SLO). ERG responses, psychophysical thresholds, and blood vessel parameters will be evaluated for significant relationships. Post-receptor function, assessed with the multifocal ERG, which tests small, discrete central retinal regions, will be compared to retinal layer thickness, cone packing geometry, and visual acuity in the older subjects. The longitudinal study of infants and young children will advance our understanding of the dynamic reorganization of the ROP post-receptor retina. The cross-sectional study of older subjects will allow us to further delineate the role of the retina in constraining visual thresholds. This project will provide new insights into mechanisms regulating visual development in ROP and, by defining retinal risk factors for visual deficits, lay the groundwork for improved clinical management of children with a history of ROP. PUBLIC HEALTH RELEVANCE: Retinopathy of prematurity (ROP) is a leading cause of visual impairment in children worldwide; many ROP patients are at risk for life-long poor vision. We use tests of retinal function and structure to identify mechanisms that control the visual development in young ROP patients. Our research will lead to new insights about the ROP disease process which will lead to improved management and treatment for ROP patients.